The problem: Active pulmonary tuberculosis (TB) is a leading cause of death from infectious disease throughout the world. Two billion people, one third of the world's population, are infected with Mycobacterium tuberculosis and 1.6 million died from the disease in 2005. Sputum microscopy and culture remains the mainstay of laboratory diagnosis, accompanied more recently by nucleic acid amplification tests (NAAT). However, sputum culture may require several weeks' incubation, while NAAT is rapid but expensive. An ideal diagnostic test would be sensitive and specific for active pulmonary TB, non-invasive, suitable for use in low- resource countries, faster than sputum culture, and less expensive than NAAT. A new solution to the problem: Mycobacteria manufacture unique volatile organic compounds (VOCs) as metabolites in vitro. A sensitive breath test employing gas chromatography-mass spectrometry (GC-MS) identified VOC biomarkers of active pulmonary TB similar to VOC metabolites of M. tuberculosis detected in vitro. BreathLink is a new point-of-care breath test employing GC with surface acoustic wave detection (GC- SAW), and it delivers results in six minutes. In a multicenter study in India, UK, and the Philippines, BreathLink identified active pulmonary TB with 98% sensitivity and 50% specificity. The high sensitivity of the BreathLink suggests that it could be used as a rule out test to identify the majority without TB. Experimental plans: BreathLink will be validated at medical centers in India and the Philippines for its ability to rule out subjects who are not infected with active pulmonary TB. I the Phase I (unblinded) study, the rule out cutoff points will be validated by comparison to the outcomes of chest x-ray and with sputum testing with microscopy, culture and NAAT. In the Phase II blinded study, a larger study will be performed with view to confirming the efficacy of BreathLink as a screening rule out test for active pulmonary TB. Potential impact of the research: If confirmed as effective, a rule out breath test could reduce the current high cost of finding new cases of active pulmonary TB, and dramatically reduce the deaths and disabilities that TB now causes in high-burden countries where health care dollars are scarce.